CXC-chemokines stimulate invasion and chemotaxis in prostate carcinoma cells through the CXCR2 receptor

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Abstract

BACKGROUND. Metastasis of prostate carcinoma requires invasion through the basement membrane, a thin extracellular matrix that underlies the epithelial cells, which must be breached by tumor cells invading into surrounding tissue. The CXC-chemokines, which have been shown to promote the migration of neutrophils and carcinoma cells, are candidates to influence prostate carcinoma-cell invasion. METHODS. CXC-chemokines were examined for the ability to stimulate prostate cell line PC3 invasion in vitro through a reconstituted basement membrane and long-term migration and short-term adhesion to laminin, a major component of the basement membrane. RESULTS. PC3 cells responded to IL-8 and GROα with a 1.6-2-fold increase in invasion through reconstituted basement membrane. A corresponding 2-3-fold increase in chemotaxis toward IL-8 and GROa was seen on laminin. Anti-CXCR2 antibody inhibited IL-8-stimulated migration. Expression levels of the β1 integrins were not changed by IL-8, and α6β1 integrin was used for both stimulated and baseline migration. In addition to the increases in migration and invasion, 2-6-fold transient increases in adhesion on laminin were seen with both IL-8 and GROα. CONCLUSIONS. These results suggest that the CXC- chemokines stimulate migration and invasion in part by altering the activation state of the β1 integrins. The CXC-chemokines act on prostate carcinoma cells through the CXCR2 receptor to promote behavior important for metastasis, and as such may be important in prostate carcinoma progression and metastasis.

Original languageEnglish (US)
Pages (from-to)78-88
Number of pages11
JournalProstate
Volume41
Issue number2
DOIs
StatePublished - 1999

Keywords

  • Basement membrane
  • Cell adhesion
  • Integrins
  • Interleukin 8
  • Laminin

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